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Wu, C.* ; Borné, Y.* ; Gao, R.* ; López Rodriguez, M.* ; Roell, W.C.* ; Wilson, J.M.* ; Regmi, A.* ; Luan, C.* ; Aly, D.M.* ; Peter, A. ; Machann, J. ; Staiger, H. ; Fritsche, A. ; Birkenfeld, A.L. ; Tao, R.* ; Wagner, R. ; Canouil, M.* ; Hong, M.G.* ; Schwenk, J.M.* ; Ahlqvist, E.* ; Kaikkonen, M.U.* ; Nilsson, P.* ; Shore, A.C.* ; Khan, F.* ; Natali, A.* ; Melander, O.* ; Orho-Melander, M.* ; Nilsson, J.* ; Häring, H.-U. ; Renström, E.* ; Wollheim, C.B.* ; Engström, G.* ; Weng, J.* ; Pearson, E.R.* ; Franks, P.W.* ; White, M.F.* ; Duffin, K.L.* ; Vaag, A.A.* ; Laakso, M.* ; Stefan, N. ; Groop, L.* ; De Marinis, Y.*

Elevated circulating follistatin associates with an increased risk of type 2 diabetes.

Nat. Commun. 12:6486 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Activin-a; Binding-protein; P446l Variant; Glucokinase; Myostatin; Glucose; Triglyceride; Mice; Gene
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 6486 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
Förderungen Lund University
DOI 10.1038/s41467-021-26536-w
WOS ID WOS:000717009800001
Scopus ID 85118927999
PubMed ID 34759311
Erfassungsdatum 2021-12-03
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